The More Difficult Road to Death: Terminal Delirium

Terminal delirium. An agitated delirium may be the first sign to herald the “difficult road to death.” It frequently presents as confusion, restlessness, and/or agitation, with or without day-night reversal.[23] To the family and professional caregivers who do not understand it, agitated terminal delirium can be very distressing. Although previous care may have been excellent, if the delirium continues to be misdiagnosed or unmanaged, family members will likely remember a horrible death, “in terrible pain,” and cognitively impaired “because of the drugs,” and they may worry that their own death will be the same. Bruera and associates[26] have documented the distressing impact of delirium on patients and families.

In anticipation of the possibility of terminal delirium, educate and support family and professional caregivers to understand its causes, the finality and irreversibility of the situation, and approaches to its management. It is particularly important that all onlookers understand that what the patient experiences may be very different from what they see.

If the patient is not assessed to be imminently dying, it may be appropriate to evaluate and try to reverse such treatable contributing factors as pain, urinary retention, and severe constipation or impaction. The treatment of reversible delirium is to find and correct reversible causes.[25] The medication class of first choice for symptomatic management of reversible delirium is the neuroleptics.[26,27]

On the other hand, irreversible delirium can also affect patients in the final hours of living. In this setting, it is referred to as “irreversible terminal delirium.”[28,29] Irreversible delirium does not respond to conventional treatments for causes of reversible delirium. Delirium, however, can be managed with medications and support of the family. Focus on the management of the symptoms associated with terminal delirium in order to settle the patient and the family.[30]

When moaning, groaning, and grimacing accompany the agitation and restlessness, these symptoms are frequently misinterpreted as physical pain.[31] However, it is a myth that uncontrollable pain suddenly develops during the last hours of life when it has not previously been a problem. Although a trial of opioids may be beneficial in the unconscious patient whose possible pain may be difficult to assess, clinicians should remember that opioids can accumulate and add to delirium when renal clearance is poor.[32,33] If a trial of opioids does not relieve the agitation or makes the delirium worse by increasing agitation or precipitating myoclonic jerks or seizures (rare), then pursue alternative therapies directed at suppressing the symptoms associated with delirium.

Currently, no studies specifically address the management of terminal delirium. Palliative experts base their treatment recommendations on the goals of treatment and the mechanisms of action of classes of medication. Benzodiazepines are generally not recommended for first-line management of delirium, especially if the delirium is thought to be reversible, because they can worsen delirium and cause paradoxical excitation, especially in the elderly.[34] However, because they are anxiolytics, amnestics, skeletal muscle relaxants, and antiepileptics,[35] benzodiazepines are recommended by palliative care experts for the management of irreversible terminal delirium when the goal of therapy is sedation. Benzodiazepines are also the medication class of first choice for management of delirium complicated by seizures or caused by alcohol or sedative withdrawal.[36] Common starting doses are:

Lorazepam: 1-2 mg as an elixir or a tablet predissolved in 0.5-1.0 mL of water and administered against the buccal mucosa every hour as needed until agitation subsides. Most patients will be controlled with 2-10 mg per 24 hour period. Lorazepam can then be given in divided doses, every 3-4 hours, to keep the patient calm. For extremely agitated patients, high doses of lorazepam, 20-50+ mg per 24 hours, may be required.

Midazolam: 1-5 mg/hour subcutaneously or intravenously by continuous infusion, preceded by repeated loading boluses of 0.5 mg every 15 minutes to effect, may be a rapidly effective alternative.

Barbiturates or propofol have been suggested as alternatives for management of refractory agitation.[37,38] Seizures, which can rarely accompany terminal delirium, can be managed with high doses of benzodiazepines or alternatively with other antiepileptics such as intravenous phenytoin, subcutaneous fosphenytoin, or phenobarbital 60-120 mg rectally, intravenously, or intramuscularly (as a last resort if there is no intravenous access) every 10-20 minutes as needed until control is established.

If benzodiazepines cause paradoxical excitation, the patient may require neuroleptic medications to control delirium. Haloperidol has fewer sedating and hypotensive effects, but in bedbound patients in whom sedation is desirable, chlorpromazine is a better choice:

Chlorpromazine: 10-25 mg orally or rectally every 60 minutes or subcutaneously/intravenously every 30 minutes until agitation is controlled. Titrate to effect, then give the summed dose nightly to every 6 hours to maintain control.[39]

Haloperidol: 0.5-2.0 mg intravenously every 10 minutes, subcutaneously every 30 minutes, or rectally every hour until agitation is controlled (titrate to effect, then give the summed dose nightly to every 6 hours to maintain control).[40]